N-glycosylation stabilizes MerTK and promotes hepatocellular carcinoma tumor growth

doi:10.1016/j.redox.2022.102366

科研成果详情

题名	N-glycosylation stabilizes MerTK and promotes hepatocellular carcinoma tumor growth
作者	Liu, Yongzhang1; Lan, Linhua1,2; Li, Yujie1,3; Lu, Jing 4; He, Lipeng 1,3; Deng, Yao 1,3; Fei, Mingming 1; Lu, Jun-Wan 1; Shangguan, Fugen1,2; Lu, Ju-Ping 1; Wang, Jiaxin1,3; Wu, Liang5; Huang, Kate5; Lu, Bin 3,6
发表日期	2022-08
发表期刊	REDOX BIOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	MerTK N-Glycosylation Hepatocellular Carcinoma Oxidative phosphorylation Warburg Effect
其他关键词	RECEPTOR TYROSINE KINASE ; THERAPEUTIC TARGET ; CANCER STATISTICS ; DOWN-REGULATION ; LIVER FIBROSIS ; EXPRESSION ; CELLS ; SITE ; PROTOONCOGENE ; PROLIFERATION
摘要	Despite the evidences of elevated expression of Mer tyrosine kinase (MerTK) in multiple human cancers, mechanisms underlying the oncogenic roles of MerTK in hepatocellular carcinoma (HCC) remains undefined. We explored the functional effects of MerTK and N-Glycosylated MerTK on HCC cell survival and tumor growth. Here, we show that MerTK ablation increases reactive oxygen species (ROS) production and promotes the switching from glycolytic metabolism to oxidative phosphorylation in HCC cells, thus suppressing HCC cell proliferation and tumor growth. MerTK is N-glycosylated in HCC cells at asparagine 294 and 454 that stabilizes MerTK to promote oncogenic transformation. Moreover, we observed that nuclear located non-glycosylated MerTK is indispensable for survival of HCC cells under stress. Pathologically, tissue microarray (TMA) data indicate that MerTK is a pivotal prognostic factor for HCC. Our data strongly support the roles of MerTK N- glycosylation in HCC tumorigenesis and suggesting N-glycosylation inhibition as a potential HCC therapeutic strategy.
资助项目	National Natural Science Foundation of China [31771534, 31570772]; Wenzhou Munic- ipal Science and Technology Bureau grant [Y2020178]; Scientific Research Foundation of University of South China [211RJC002]
出版者	ELSEVIER
出版地	AMSTERDAM
ISSN	2213-2317
卷号	54 页码:102366
DOI	10.1016/j.redox.2022.102366
页数	16
WOS类目	Biochemistry & Molecular Biology
WOS研究方向	Biochemistry & Molecular Biology
WOS记录号	WOS:000818759200003
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	35728303
SCOPUSEID	2-s2.0-85132815660
通讯作者地址	[Lu, Bin]Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Hengyang Medical School,University of South China,Hunan,Hengyang,421001,China
Scopus学科分类	Organic Chemistry
TOP期刊	TOP期刊
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/154298
专题	检验医学院（生命科学学院、生物学实验教学中心）附属第一医院检验医学院（生命科学学院、生物学实验教学中心）_Attardei线粒体研究院
通讯作者	Lu, Bin
作者单位	1.Protein Quality Control and Diseases Laboratory,Zhejiang Provincial Key Laboratory of Medical Genetics,Key Laboratory of Laboratory Medicine,Ministry of Education,School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 2.Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China; 3.Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Hengyang Medical School,University of South China,Hunan,Hengyang,421001,China; 4.Department of Laboratory Medicine,The First People's Hospital of Jingzhou,The First Affiliated Hospital of Yangtze University,Hubei,Jingzhou,434000,China; 5.Department of Pathology,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China; 6.Attardi Institute of Mitochondrial Biomedicine,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
第一作者单位	检验医学院（生命科学学院、生物学实验教学中心）
第一作者的第一单位	检验医学院（生命科学学院、生物学实验教学中心）
推荐引用方式 GB/T 7714	Liu, Yongzhang,Lan, Linhua,Li, Yujie,et al. N-glycosylation stabilizes MerTK and promotes hepatocellular carcinoma tumor growth[J]. REDOX BIOLOGY,2022,54:102366.
APA	Liu, Yongzhang., Lan, Linhua., Li, Yujie., Lu, Jing., He, Lipeng., ... & Lu, Bin. (2022). N-glycosylation stabilizes MerTK and promotes hepatocellular carcinoma tumor growth. REDOX BIOLOGY, 54, 102366.
MLA	Liu, Yongzhang,et al."N-glycosylation stabilizes MerTK and promotes hepatocellular carcinoma tumor growth".REDOX BIOLOGY 54(2022):102366.